Phytoestrogenic Activities of Daucane Esters from Ferulago campestris on MCF-7 Cell Lines

Introduction: Daucane sesquiterpenes are natural compounds possessing several biological activities thus being considered as good pharmacophoric models for the study of novel bioactive agents. Daucane esters are sesquiterpene compounds that are typical of Ferula and related species. Derivatives were reported from different Ferula and Ferulago species and the various natural compounds possess a common structure characterized by fused hepta- and penta- atomic rings with different hydroxylated positions that could be esterified by organic acids. Daucane obtained from roots of Ferulago campestris and Ferula glauca were previously studied as antiproliferative and antiapoptotics in human tumor cell lines. Hence, phytoestrogenic activities of daucane esters isolated from F. campestris were examined on MCF-7 cell lines using the Real-Time XCELLigence impedance analysis. Methods: Extracted and purified daucane esters tested on MCF-7 cells to measure cell growth and proliferation using real-time xCELLigence cell impedance analysis (Roche Applied Science) on disposable E-plates with 48 (16x3) wells containing integral sensor electrode arrays. This method uses impedance technology as an indicator of cell attached (1,2). Results: We tested 13 different natural daucane derivatives for the ability to interact with estrogenic receptor in a cellular model. Concentrations were selected as 6 and 25 µg/mL in order to avoid possible cytotoxic effects of the tested compounds in the assay conditions. Among the tested compounds (1-13) applied at 6 µg/mL concentrations for the assessment of MCF-7 cell proliferation after 24, 48 and 72 hours, compounds 4, 6, 7 and 9-13 exhibited significant increases in cell index (CI) values relative to controls. However, it was estimated that not all of these increases were depending on time of exposure elapsed. Conclusions: The obtained data revealed moderate effect for several of the considered daucane esters. Surprisingly the compound 12 the only compound of the series that present a free phenolic group was not active while severeal derivatives possessing more lipophylic or non aromatic ester substitutions (as compounds 4, 6, 7, 9, 11, 13) presented significant effects in the used model